Muscle atrophy is caused by a gradual decrease in muscle mass and refers to muscle weakness and degeneration (Cell, 119 (7): 907-910, 2004). Muscle atrophy is accelerated by inactivity, oxidative stress, and chronic inflammation, while weakening muscular function and athletic performance (Clinical Nutrition, 26 (5): 524-534, 2007). The most important factor determining muscular function is muscle mass, which is maintained by a balance of protein synthesis and degradation. Muscular atrophy is caused when protein degradation occurs greater than protein synthesis (The International Journal of Biochemistry and Cell Biology, 37 (10): 1985-1996, 2005).
While the size of a muscle is regulated by intracellular signaling pathways leading to anabolism or catabolism within the muscle, the synthesis of muscle protein increases when the signaling reactions inducing the synthesis of muscle protein are greater than those inducing the degradation of the muscle protein. This occurs as an increase in the number of muscle fibers (hyperplasia) or an increase in the size of muscle (hypertrophy) due to the increase in muscle protein (The Journal of Sports Science, 20 (3): 1551-1561, 2011). Factors involved in muscle protein synthesis induce protein synthesis by phosphorylating downstream proteins based on the stimulation of phosphatidylinositol-3 kinase (PI3K)/Akt pathway in muscle cells. The activation of the mammalian target of rapamycin (mTOR) by PI3K/Akt signaling is recognized as a central growth signaling factor that integrates various growth signals in the cell. mTOR induces muscle protein synthesis by activating two factors that initiate mRNA translation, i.e. 4E-binding protein (4EBP1) and phosphorylated 70-kDa ribosomal S6 kinase (p70S6K), contributing to increase in muscle mass (The Korea Journal of Sports Science, 20 (3): 1551-1561, 2011; The International Journal of Biochemistry and Cell Biology, 43 (9): 1267-1276, 2011). Conversely, when the transcription factor forhead box (FoxO) migrates from the cytoplasm to the nucleus, it increases the expression of the E3 ubiquitin ligase, atrogin-1 and MuRF-1 which are involved in proteolysis (Disease Models and Mechanisms, 6:25-39, 2013). Increasing the expression level of these proteins promotes protein degradation in muscles, resulting in reduced muscle mass. Thus, the activation of mTOR activity and inhibition of atrogin-1 and MuRF-1 expression increase muscle mass by increasing the amount of muscle protein.
Muscle cell differentiation and muscle formation are regulated by a variety of muscle regulatory factors. Among them, MyoD initiates the expression of muscle specific genes and induces the differentiation of muscle satellite cells into myoblasts. Induction of myogenin expression by activation of MyoD is the most important factor in the fusion of myoblasts and is involved in the formation of myotubes. The muscle fibers formed through this process are bundled to finally form muscles (Cellular and Molecular Life Sciences, 70: 4117-4130, 2013).
Mori Cortex Radicis is the dried root bark of Morus alba or other plants belonging to a plant of family Moraceae and genus Morus spp. The Morus alba, which is also called as mulberry, has been reported to possess various effects such as anti-obesity (Nutrition Research and Practice, 8 (6): 613-617, 2014), anti-photoaging (Journal of Korea Society of Food Science and Nutrition, 42(11): 1744-1752, 2013), anti-diabetes (Journal of Ethnopharmacology, 100 (3): 333-338, 2005), and anti-oxidant and skin whitening effects (Food and Chemical Toxicology, 49 (4): 785-790, 2011).
Morusin and kuwanon G are flavones found primarily in Mori Cortex Radicis, respectively (Microchemical Journal, 110: 731-738, 2013). Morusin has been reported to possess such effects as anti-microbial effect (Journal of China Pharmaceutical University, 45(2): 221-226, 2014), anti-obesity effect (Molecule, 16(7): 6010-6022, 2011), and anti-cancer effect (Toxicology Letters 232(2): 490-498, 2015). In addition, it has been reported that kuwanon G possesses an anti-bacterial effect (Journal of Ethnopharmacology, 84 (2-3): 181-5, 2003; Phytomedicine, 11 (7-8): 666-672, 2004).
However, prior to the present invention, there has been no report on the prevention or treatment of muscular diseases or the improvement of muscular function of Mori Cortex Radicis, morusin, or kuwanon G.